Human Growth Hormone (HGH) and testosterone supplementation have shown promising effects in patients with heart failure despite numerous small, short-term clinical trials showing mixed results. Selected patients may benefit from supplementation in addition to conventional therapy, in particular patients with documented hormonal deficiency (below or in the low-normal range). Patients with suspected HGH resistance may warrant pretreatment screening prior to supplementation to adjust dosing and possible direct IGF-1 administration in addition to HGH. However, from our knowledge, there are no direct studies with both HGH and IGF-1 supplementation in heart failure, thus recommendations cannot be made regarding this dual therapeutic approach.
Minimal data exist for combined therapy of HGH and testosterone in the setting of heart failure. The studies using combined HGH and testosterone supplementation were mostly conducted in older men with testosterone and IGF-1 in lower ranges of normal. One study showed promising effects on the improvement of body composition and muscle performance, while another study found no change in function, mood and body composition. However, the latter study observed improvements in balance and muscle IGF-1 gene expression. Future studies investigating combined HGH and testosterone therapy in patients with heart failure would be warranted in order to assess possible synergistic effects, which may be advantageous over monotherapy.
Testosterone treatment has been shown to exert beneficial effects in both men and women with heart failure with few adverse effects. In our patients with advanced heart failure and other comorbid conditions, we routinely screen for and treat testosterone deficiency. Approximately 20–30% of our heart failure patients, those with ventricular assist devices and patients with postorthotopic heart transplantation status, have received supplemental testosterone at some point. Anecdotally, the patients have improved nutritional status as well as improved functionality and sense of well being. Although our patients appear to show some clinical improvement with testosterone therapy, we currently do not have conclusive data to recommend testosterone therapy in heart failure patients. Despite the promising role of hormonal supplementation in Heart Failure, larger, long-term, randomized clinical trials are warranted to further assess efficacy and safety of manipulation of the hormonal imbalance in patients with chronic Heart Failure.
Patients with heart failure are often observed to have hormonal dysregulation. HGH/IGF-1 axis derangement and testosterone deficiency have been an area of great interest as an adjunctive therapy in patients with advanced heart failure. While early studies show that HGH supplementation in patients with heart failure enhances cardiac function resulting in improvement in clinical symptoms, subsequent studies did not demonstrate significant improvements in cardiac morphology, performance or clinical status. However, the studies have been small with relatively short study duration. Of note, the inconsistent data may be linked to HGH resistance in patients and this may affect the biochemical response to HGH therapy. Patients with HGH resistance were observed to have lower levels of IGF-1, thus combination therapy of both HGH and IGF-1 may be beneficial. Coadministration of HGH and IGF-1 in patients with heart failure have not been fully investigated, thus the efficacy and safety of this therapeutic approach remains uncertain.
The majority of adverse effects observed in patients on long-term HGH replacement therapy include edema, insulin resistance, arthralgia and myalgia. These adverse effects were often related to higher dosing; therefore, appropriate dosing will have to be addressed to minimize adverse effects but maximize beneficial outcomes. Because there are inconsistent data on efficacy and lack of long-term assessment on safety – large randomized clinical trials are needed to fully evaluate these issues before starting patients on HGH-replacement therapy.
Similarly, testosterone therapy in patients with heart failure shows improvement in functional status and prognosis. Multiple studies observe improvements in parameters such as LV performance, incremental shuttle walk test and mean peak oxygen consumption. The adverse effects of testosterone therapy have been associated with exacerbation of prostate cancer, atherosclerosis, unfavorable lipid profiles and polycythemia. These adverse effects were mainly observed when testosterone was administered at supraphysiological levels. Despite the positive benefits of testosterone replacement, the long-term efficacy and safety remains unclear and will need to be addressed prior to committing a patient to long-term therapy.
HGH and testosterone therapy have shown promising benefits in patients with heart failure. At present, many institutions, including our own, are actively participating in trials to reproduce the data observed in earlier studies. As more data are available and large clinical studies show consistent benefits with minimal adverse effects, hormonal supplementation may become an integral agent in the treatment of heart failure. If the benefits and safety are clearly established, patients may be prescreened for low levels of HGH and testosterone early on in their course of disease. This strategy may lead to earlier initiation of hormone therapy with hopes of improving functional status and quality of life.
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